Specific treatment for Duchenne muscular dystrophy (DMD) is not available. Prevention of new cases by abortion of at-risk fetuses is the major treatment strategy currently employed. Because they cannot be reliably differentiated, unaffected as well as affected male fetuses are aborted. The general region of the X chromosome harboring the DMD gene is now recognized to the Xp2.1. A probe that recognizes a DNA sequence deleted from the Xp2.1 region in several boys with DMD will be used in our DMD families to see if the deleted DNA sequence is linked to the DMD gene. Other DNA sequences deleted from the Xp2.1 region in our DMD cases will be isolated and characterized using recombinant DNA techniques. It is likely that these deletion sequences will be closely linked to the DMD gene, or include the DMD gene, and therefore, enable more accurate detection of affected fetuses and carrier women. Assuming that the DMD gene codes for a protein, translation of open reading frames within these DNA sequences will facilitate identification of defective (or absent) proteins specific to DMD muscle. This will provide the basis from which to develop antibodies to the abnormal DMD proteins, or alternatively, to develop antibodies against proteins that are present in normal muscle, but absent from DMD muscle. For DMD boys with a deletion, deletion probes will be used in the mother to determine the proportion of isolated DMD cases that result from new mutations, as compared to those that are inherited through carrier females. The source of the mutation in familial cases, i.e., the maternal grandmother or grandfather, can also be established. Inherited cases can theoretically be prevented by prenatal diagnosis. The long-range goals will include the linkage analysis of this sequence with other known Xp2.1 probes in our large multigenerational DMD families, accurate diagnosis of affected DMD fetuses, and development of an antibody test that will reliably distinguish DMD carrier females from noncarrier females. Finally, delineation of the proportion and the source of DMD cases resulting from new deletion mutations will be possible using deletion probes.